Identification and Expression Analysis of CD73 Inhibitors in Cervical Cancer

2020 ◽  
Vol 16 ◽  
Author(s):  
Jamshed Iqbal ◽  
Ayesha Basharat ◽  
Sehrish Bano ◽  
Syed Mobasher Ali Abid ◽  
Julie Pelletier ◽  
...  

Aims: The present study was conducted to examine the inhibitory effects of synthesized sulfonylhydrazones on the expression of CD73 (ecto-5′-NT). Background: CD73 (ecto-5′-NT) represents the most significant class of ecto-nucleotidases which are mainly responsible for dephosphorylation of adenosine monophosphate to adenosine. Inhibition of CD73 played an important role in the treatment of cancer, autoimmune disorders, precancerous syndromes, and some other diseases associated with CD73 activity. Objective: Keeping in view the significance of CD73 inhibitor in the treatment of cervical cancer, a series of sulfonylhydrazones (3a-3i) derivatives synthesized from 3-formylchromones were evaluated. Methods: All sulfonylhydrazones (3a-3i) were evaluated for their inhibitory activity towards CD73 (ecto-5′-NT) by the malachite green assay and their cytotoxic effect was investigated on HeLa cell line using MTT assay. Secondly, most potent compound was selected for cell apoptosis, immunofluorescence staining and cell cycle analysis. After that, CD73 mRNA and protein expression were analyzed by real-time PCR and Western blot. Results: Among all compounds, 3h, 3e, 3b, and 3c were found the most active against rat-ecto-5′-NT (CD73) enzyme with IC50 (µM) values of 0.70 ± 0.06 µM, 0.87 ± 0.05 µM, 0.39 ± 0.02 µM and 0.33 ± 0.03 µM, respectively. These derivatives were further evaluated for their cytotoxic potential against cancer cell line (HeLa). Compound 3h and 3c showed the cytotoxicity at IC50 value of 30.20 ± 3.11 µM and 86.02 ± 7.11 µM, respectively. Furthermore, compound 3h was selected for cell apoptosis, immunofluorescence staining and cell cycle analysis which showed promising apoptotic effect in HeLa cells. Additionally, compound 3h was further investigated for its effect on expression of CD73 using qRT-PCR and western blot. Conclusion: Among all synthesized compounds (3a-3i), Compound 3h (E)-N'-((6-ethyl-4-oxo-4H-chromen-3-yl) methylene)-4-methylbenzenesulfonohydrazide was identified as most potent compound. Additional expression studies conducted on HeLa cell line proved that this compound successfully decreased the expression level of CD73 and thus inhibiting the growth and proliferation of cancer cells.

2020 ◽  
pp. 4-7
Author(s):  
M. R. Kamala Priya ◽  
Priya R. Iyer

Doxorubicin is the most common chemotherapy drug used in cancer therapy. Its usage is associated with various side-effects. In order to overcome the challenges in Doxorubicin administration, the present study has focussed on synthesizing a drug conjugate with biosynthesized gold nanoparticles and doxorubicin. The gold nanoparticles were biosynthesized using green extracts of medicinal plants with potential anticancer activities. The nanoparticle that possesses anticancer activity was conjugated with the drug for a combinatorial effect of the nanoparticles and the drug. The in vitro cytotoxicity was checked in Vero cell line through MTT assay. The in vitro anti proliferative effects were screened against cervical cancer in HeLa cell line. Fluorescence activated cell sorting analysis was carried out to detect the difference between live and dead cell populations. The preliminary confirmation was carried out in UV-VIS spectrophotometer. The morphological characterization was carried out by SEM and stability by Zeta potential. The IC50 of the nanocompounds demonstrated anti-proliferative activity against cervical cancer similar to the chemotherapeutic drug, Doxorubicin; additionally in a much lesser concentration of the drug. The in vitro cytotoxicity exhibited high viability of cells in Vero cell line with minimum viability of 80% in all the tested concentrations. There was a synergistic effect of the nanoparticles along with the drug; thereby an enhanced therapeutic efficiency was achieved. FACS analysis showed 36% of cell death in Dox treated HeLa cells whereas 96% of cell death in Nano-Dox treated HeLa cells. Nano-Dox conjugate has demonstrated high anticancer effects than drug alone Doxorubicin. Further biosynthesized nanomaterials based drug formulation can be developed as a potential strategy in cancer therapy.


2020 ◽  
Vol 47 (8) ◽  
pp. 6135-6142
Author(s):  
Jalal Hassanshahi ◽  
Afsaneh Mirzahosseini-pourranjbar ◽  
Zahra Hajializadeh ◽  
Ayat Kaeidi

2017 ◽  
Vol 24 (4) ◽  
pp. 563-570 ◽  
Author(s):  
Hannaneh Zarrinnahad ◽  
Amir Mahmoodzadeh ◽  
Monireh Parviz Hamidi ◽  
Mehdi Mahdavi ◽  
Ali Moradi ◽  
...  

2021 ◽  
Vol 55 (2) ◽  
pp. 162-170
Author(s):  
Samaneh Kamalipooya ◽  
Amir Sabet ◽  
Fatemeh Javani Jouni ◽  
Mohammad Satari ◽  
Parviz Abdolmaleki ◽  
...  

2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Adisty Ridha Damasuri ◽  
Eti Nurwening Sholikhah ◽  
Mustofa

In our previous study, some amino chalcone derivatives have been synthesized and evaluated their cytotoxicity against breast cancer cell line T47D. Among 11 amino chalcone derivatives, ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) exhibited the most active compound.This study aimed to investigate cytotoxic activity of the ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) against cervical cell line (HeLa). The cytotoxic activitywas determined using the MTT colorimetric assay. Cisplatin was used as positive control. From this MTT method, inhibitory concentration 50% (IC50) values were determined by probit analysis based on the relationship between log concentrations versus the percentage of cells growth inhibition.The results showed that the IC50 of ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) and cisplatinwere 22.75 ± 19.13 μg/mL and 14.96±1.08 μg/mL, respectively. In conclusion, the ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) has moderate cytotoxic activity against HeLa cell line based on National Cancer Institute (NCI) criteria.


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